bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 4, 2023
ABSTRACT
Tight
junctions
are
a
barrier-forming
cell-cell
adhesion
complex
and
have
been
proposed
to
regulate
cell
proliferation.
However,
the
underlying
mechanisms
not
well
understood.
Here,
we
used
cells
deficient
in
junction
scaffold
ZO-1
alone
or
together
with
its
paralog
ZO-2,
which
disrupts
junctional
barrier.
We
found
that
knockout
increased
proliferation,
loss
of
density-dependent
proliferation
control,
promoted
death.
These
phenotypes
were
enhanced
by
double
ZO-1/ZO-2
knockout.
Increased
was
dependent
on
YAP
ZONAB,
two
transcriptional
regulators.
stimulated
nuclear
translocation
activity
without
changes
Hippo-dependent
phosphorylation.
Knockout
TANK-binding
Kinase
1
(TBK1)
activation
expression
RhoA
activator
GEF-H1.
Knockdown
ZO-3,
another
interacting
ZO1,
sufficient
induce
GEF-H1
activity.
GEF-H1,
TBK1,
mechanotransduction
at
focal
adhesions
required
for
YAP/TEAD
ZO-1-deficient
cells.
Thus,
controls
Hippo-independent
activating
GEF-H1-
TBK1-regulated
mechanosensitive
signalling
network.
Journal of Cell Science,
Год журнала:
2024,
Номер
137(9)
Опубликована: Май 1, 2024
ABSTRACT
Tight
junctions
(TJs)
are
specialized
regions
of
contact
between
cells
epithelial
and
endothelial
tissues
that
form
selective
semipermeable
paracellular
barriers
establish
maintain
body
compartments
with
different
fluid
compositions.
As
such,
the
formation
TJs
represents
a
critical
step
in
metazoan
evolution,
allowing
multicompartmental
organisms
true,
barrier-forming
epithelia
endothelia.
In
six
decades
have
passed
since
first
observations
by
transmission
electron
microscopy,
much
progress
has
been
made
understanding
structure,
function,
molecular
composition
regulation
TJs.
The
goal
this
Perspective
is
to
highlight
key
concepts
emerged
through
research
future
challenges
lie
ahead
for
field.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2025,
Номер
44(1)
Опубликована: Фев. 7, 2025
Abstract
The
gut
microbiota
plays
a
crucial
role
in
safeguarding
host
health
and
driving
the
progression
of
intestinal
diseases.
Despite
recent
advances
remarkable
correlation
between
dysbiosis
extraintestinal
cancers,
underlying
mechanisms
are
yet
to
be
fully
elucidated.
Pathogenic
microbiota,
along
with
their
metabolites,
can
undermine
integrity
barrier
through
inflammatory
or
metabolic
pathways,
leading
increased
permeability
translocation
pathogens.
dissemination
pathogens
circulation
may
contribute
establishment
an
immune-suppressive
environment
that
promotes
carcinogenesis
organs
either
directly
indirectly.
oncogenic
cascade
always
engages
disruption
hormonal
regulation
responses,
induction
genomic
instability
mutations,
dysregulation
adult
stem
cell
proliferation.
This
review
aims
comprehensively
summarize
existing
evidence
points
potential
malignant
transformation
such
as
liver,
breast,
lung,
pancreas.
Additionally,
we
delve
into
limitations
inherent
current
methodologies,
particularly
challenges
associated
differentiating
low
loads
gut-derived
microbiome
within
tumors
from
sample
contamination
symbiotic
microorganisms.
Although
still
controversial,
understanding
contribution
translocated
metabolites
pathological
continuum
chronic
inflammation
could
offer
novel
foundation
for
development
targeted
therapeutics.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
Abstract
Disruption
of
the
intestinal
epithelial
barrier
results
in
increased
permeability
and
is
a
key
factor
onset
progression
Crohn's
disease
(CD).
The
protein
SPARC
primarily
involved
cell
interaction
migration,
but
its
specific
role
remains
unclear.
This
study
demonstrates
that
significantly
overexpressed
both
CD
patients
murine
models
colitis.
Furthermore,
mice
deficient
exhibits
resistance
to
chemically
induced
colitis,
phenomenon
associated
with
modulation
barrier‐associated
proteins.
Mechanistically,
it
elucidated
competitively
binds
OTUD4
conjunction
MYD88,
facilitating
translocation
p65
from
cytoplasm
nucleus
subsequent
activation
p65‐MLCK/MLC2
pathway,
thereby
compromising
integrity.
Additionally,
identified
elevated
expression
regulated
via
METTL3‐YTHDF1
axis.
These
findings
indicate
levels
are
colitis‐induced
mice,
leading
damage
through
direct
MYD88/p65/MLCK/MLC2
signaling
pathway.
Consequently,
targeting
or
OTUD4/MYD88/p65/MLCK/MLC2
axis
may
offer
novel
insights
into
molecular
mechanisms
underlying
represent
potential
therapeutic
strategy.
Biology,
Год журнала:
2025,
Номер
14(3), С. 267 - 267
Опубликована: Март 6, 2025
Epithelial
linings
are
crucial
for
the
maintenance
of
physiological
barriers.
The
intestinal
epithelial
barrier
(IEB)
consists
enterocytes
through
tight
junctions
and
mucus-secreting
cells
can
undergo
modifications
throughout
life.
To
reproduce
as
closely
possible
IEB
main
features
over
time,
in
vitro
co-cultures
Caco2/HT-29
70/30
formed
by
parental
Caco2
HT-29
sub-cultivated
more
than
40
passages
were
set
up.
measurements
transepithelial
electrical
resistance
(TEER)
identified
two
populations:
TEER
(PC)
with
values
>
50
Ωcm2
fewer
passages,
leaky
(LC)
<
passages.
In
LC,
paracellular
permeability
increased
parallel.
By
immunofluorescence
Western
blot
analysis,
an
increase
claudin
2
was
observed
LC
vs.
PC,
no
differences
occludin
expression.
MUC-2
immunoreactivity
stronger
PC
LC.
also
showed
enhanced
vulnerability
to
TNFα+IFN-γ.
These
results
morpho-functional
reported
human
leaky/aged
gut
support
usefulness
our
cell
model
studying
molecular
processes
underlying
these
testing
drug/nutraceutical
treatments
ameliorate
aging.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 16, 2024
In
patients
with
rheumatoid
arthritis
(RA),
intestinal
flora
imbalance
and
butyrate
metabolism
disorders
precede
clinical
are
associated
the
pathogenesis
of
RA.
This
can
alter
immunology
permeability
mucosa,
leading
to
damage
barrier.
this
context,
bacteria
their
metabolites
enter
bloodstream
reach
distant
target
tissues
host,
resulting
in
local
inflammation
aggravating
arthritis.
Additionally,
is
also
exacerbated
by
bone
destruction
immune
tolerance
due
disturbed
differentiation
osteoclasts
adaptive
cells.
Of
note,
a
metabolite
flora,
which
not
only
locally
inhibits
immunity
targets
zonulin
tight
junction
proteins
alleviate
barrier-mediated
but
autoantibodies
balances
responses
T
B
lymphocytes
throughout
body
repress
erosion
inflammation.
Therefore,
key
intermediate
linking
host.
As
result,
restoring
butyrate-producing
capacity
using
exogenous
potential
therapeutic
strategies
for
RA
future.
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 22, 2025
Background
Periplanta
americana
extract
(PAE),
a
traditional
Chinese
medicine
(TCM)
from
Shen
Nong
Ben
Cao
Jing
,
has
been
used
to
treat
ulcerative
colitis
(UC),
various
types
of
wounds
and
ulcers,
infantile
malnutrition,
palpitation,
asthma,
so
on.
However,
the
exact
mechanisms
PAE
in
UC
have
still
not
fully
revealed.
The
study
aims
explore
therapeutic
effects
UC.
Methods
efficacy
was
evaluated
using
DSS-induced
mice
model
colon
inflammation
mucosal
barrier
were
comprehensively
assessed.
Furthermore,
Network
pharmacological
analysis
utilized
identify
potential
targets
signaling
pathways
treatment.
proportion
markers
Th17
Treg
cells
spleen
examined.
signal
transduction
detected
vivo
.
In
vitro
an
activated
Notch1-mediated
Th17/Treg
modeled,
effect
on
epithelial
cell
Results
mitigated
intestinal
damage
mice.
showed
that
intervention
by
may
be
closely
related
differentiation,
IL-17
pathway,
cytokine-cytokine
receptor
interaction.
Mechanistically,
regulated
balance
inhibited
Notch1/Math1
pathway
alleviated
imbalance
Jurkat
T
cells.
After
notch1-activated
co-cultured
with
HCoEpic
cells,
expressions
Occludin,
ZO1
higher
Conclusion
could
alleviate
UC,
which
are
inhibition
Notch1
regulation
balance.
might
candidate
agent
for
